Children and adolescents meeting DSM-III-R criteria for schizophrenia with onset of psychosis prior to age 12 are available and five subjects have participated to date in this study of the phenomenology, neurobiology and pharmacologic response of childhood onset schizophrenia. Diagnostic reliability has been established and two subgroups may emerge. Pilot family/genetic data indicates one cause is familial and a second subject had a chromosomal aberration. Autonomic measures parallel adult schizophrenia. MRI abnormalities have been found in the brainstem and PET indicates hypofrontality. Safety and efficacy of clozapine in this age group was demonstrated in an open trial in three subjects. Two subjects have entered an ongoing double-blind comparison of haloperidol and clozapine. In an ongoing double-blind comparison of clomipramine, desipramine and placebo children with autistic disorder show a selective response to clomipramine supporting a serotonergic disturbance in this disorder.